chr15-22853374-C-CT

Variant names:

• chr15-22853374-C-CT
• rs35568106
• NM_030922.7:c.196+123dupT

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_030922.7(NIPA2):​c.196+123dupT variant causes a intron change. The variant allele was found at a frequency of 0.0507 in 379,184 control chromosomes in the GnomAD database, including 11 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0070 (11 hom., cov: 23)
  • Exomes 𝑓: 0.075 (0 hom.)
• Consequence: NIPA2 NM_030922.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.79
• Publications: 1 publications found

Genes affected

NIPA2 (HGNC:17044): (NIPA magnesium transporter 2) This gene encodes a possible magnesium transporter. This gene is located adjacent to the imprinted domain in the Prader-Willi syndrome deletion region of chromosome 15. Alternate splicing results in multiple transcript variants. Pseudogenes of this gene are found on chromosomes 3, 7 and 21.[provided by RefSeq, May 2010]

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BS2: High Homozygotes in GnomAd4 at 11 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NIPA2	NM_030922.7	c.196+123dupT		intron_variant	Intron 5 of 7	ENST00000337451.8	NP_112184.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NIPA2	ENST00000337451.8	c.196+106_196+107insT		intron_variant	Intron 5 of 7	5	NM_030922.7	ENSP00000337618.3

Frequencies

GnomAD3 genomes AF: 0.00699 AC: 959 AN: 137216 Hom.: 11 Cov.: 23

Gnomad AFR AF: 0.0161

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00432

Gnomad ASJ AF: 0.0122

Gnomad EAS AF: 0.00404

Gnomad SAS AF: 0.00710

Gnomad FIN AF: 0.00272

Gnomad MID AF: 0.00685

Gnomad NFE AF: 0.00285

Gnomad OTH AF: 0.00536

GnomAD4 exome AF: 0.0754 AC: 18249 AN: 241944 Hom.: 0 AF XY: 0.0755 AC XY: 9874 AN XY: 130774

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.0779 AC: 469 AN: 6020

American (AMR) AF: 0.0528 AC: 488 AN: 9242

Ashkenazi Jewish (ASJ) AF: 0.0754 AC: 492 AN: 6528

East Asian (EAS) AF: 0.0765 AC: 1175 AN: 15358

South Asian (SAS) AF: 0.0708 AC: 1569 AN: 22170

European-Finnish (FIN) AF: 0.0731 AC: 1050 AN: 14372

Middle Eastern (MID) AF: 0.0541 AC: 64 AN: 1184

European-Non Finnish (NFE) AF: 0.0779 AC: 12025 AN: 154454

Other (OTH) AF: 0.0727 AC: 917 AN: 12616

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.00698 AC: 958 AN: 137240 Hom.: 11 Cov.: 23 AF XY: 0.00715 AC XY: 472 AN XY: 65990

African (AFR) AF: 0.0160 AC: 596 AN: 37202

American (AMR) AF: 0.00431 AC: 58 AN: 13442

Ashkenazi Jewish (ASJ) AF: 0.0122 AC: 40 AN: 3284

East Asian (EAS) AF: 0.00405 AC: 19 AN: 4686

South Asian (SAS) AF: 0.00713 AC: 31 AN: 4350

European-Finnish (FIN) AF: 0.00272 AC: 21 AN: 7724

Middle Eastern (MID) AF: 0.00373 AC: 1 AN: 268

European-Non Finnish (NFE) AF: 0.00286 AC: 182 AN: 63532

Other (OTH) AF: 0.00532 AC: 10 AN: 1878

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		3.8

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs35568106; hg19: chr15-23019694;